This application is for continued support of the Digestive Diseases Research Core Center (DDRCC) at Washington University St. Louis, focusing on regulatory factors in the GI tract. We believe that by gaining a fundamental understanding of the regulation of GI-processes, we will be able to more rationally prevent and treat GI diseases, including peptic ulcer, inflammatory bowel disease and acute and chronic liver diseases. Our philosophy is that the most effective way to develop new opportunities in digestive diseases related research is to invest in motivated individuals, especially at early stages of their careers. Consequently, the Washington University DDRCC focuses on mentoring and training students, residents, fellows and junior faculty with the goal of fostering new independent investigators in digestive diseases-related research. This center has excelled in developing young independent researchers though our Pilot/Feasibility Program. Our success can also be measured by the fact that both total extramural and NIDDK digestive diseases-related research base has more than doubled since the center's inception in 2000. The programmatic themes of the Digestive Diseases Research Core Center reflect its outstanding research base and are: 1.) Host-microbial interactions, inflammation and mucosal immunity; 2.) Gut development, differentiation and epithelial renewal; 3.) Nutrient transport, metabolism and signaling; 4.) Hepatobiliary metabolism, injury-repair. Washington University DDRCC investigators have been at the forefront in each of these programmatic themes. Partnership between a junior DDRCC investigator and clinical gastroenterologist has led to a novel paradigm in the treatment of inflammatory bowel disease. DDRCC investigators have pioneered the use of DNA microarray analyses of laboratory and clinical human samples to identify novel biomarkers and mediators in each of the four programmatic themes. These successes have in turn prompted us to propose to expand the Research Core services, including gnotobiotics, laser capture microdissection, DNA microarray, proteomics and bioinformatics. The goals of this DDRCC are to continue to promote and enhance interdisciplinary digestive disease research through its four research core facilities (Murine Models, Morphology, Functional Genomics and Proteomics).